We report here that topical application of clonidine displacing substance (CDS), an endogenous brain extract, directly in the nucleus reticularis lateralis (NRL) region of anaesthetized cats regularly produced hypertension. CDS (5 units) increased the mean blood pressure by 40 +/- 8%. Pretreatment of anaesthetized rabbits with intracisternal CDS (500 units) shifted to the right the dose-response curve obtained with clonidine alone injected the same way. This brain extract might be considered as an endogenous antagonist for the hypotensive effects of clonidine at least in the NRL region.